Compounds of the xanthene series



Patented Mar. 21, 1933 UNITED STATES Leeann PATENT IOFFEQE WERNERSCHUL-EMANN, O3? VOHWINKEL, NEAR ELBERFELD, FRITZ MIETZSCH, OFELBERFELD, GERMANY, AND AUGUST WINGLER,' WESTFIELD, NEW JERSEY,ASSIGNORS T WINTHRQP CHEMICAL COMPANY, INC., OF NEW YORK, N. Y., .A.GOR- POBATION or NEW YORK comrounns or THE XANTHENE snares No Drawing.Application filed November 15, 1929, Serial No. 407,559, and GermanySeptember 11, 1924,

pounds of the xanthene series, more particularly it relates toxanthenes, being at least once substituted in the benzene nuclel by asubstituent of the general formula:

wherein a: stands for hydrogen, or, for example, an alkyl group, anaminoalkyl group, or substituted aminoalkyl group, such as amono-alkyl-aminoalkyl group or dialkylaminoalkyl group, R stands for analkylene residue, in which the hydrogen atoms may be replaced bymonovalent substituents, for example, by the hydroxy group, R and R 2 9stand for alkyl groups which may be substituted, for example, by anamino group,and wherein the Xanthene nucleus may be further substituted,for example, by alkyl, alkoxy,

V phenyl, halogen and the like.

ly valuable products. a

The manufacture of our new compounds can be effected in several ways;for instance, an amino derlvatlve of axanthene may be The presentinvention relates to new com caused to be acted upon by an aminoalkyhalide having the general formula:

p a R1 y-RrN a wherein 3 represents a halogen atom, R an alkyleneresidue vthe hydrogen atoms of which may be replaced by m-onovalentsubstituents, such as the hydroxy group, R andR stand for hydrogen oralkyl groups which may be substituted, for' example, by amino groups.

Instead of the aminoalkyl halide one may use in this process the salt ofan aminoalkyl which may be replaced by monovalent subcan be furthermoreeffected by converting.

suchaminocompounds as are suitable interv stituents, such as the hydroxygroup, B 'and '1 mediate products for the manufacture of aminoiderivatives of the Xanthene into aminoalkylamino derivatives andsubsequently transforming thev latter into the correspond ing Xanthenecompounds according to known methods. 'lVe are aware of the-fact thatseveral other methods for preparing our new compounds are obvious which,however, we do not mention specifically.

The followingex'amples will illustrate our. invention, without limitingit thereto:

"For the preparation of meta-hydroxy-N- (diethyl-amino ethyl ethyl)aminobenzene 102 grams of meta-oXy-N-ethylaniline are dissolved in 150ccm of benzene on the waterbath, 100 grams of diethylamino-ethylchloridein 150 0cm of benzene are added and the, whole is heated to boiling forone day. On cooling, the benzene is decanted and the free base isliberated from the aqueous layer by the addition of potassium carbonateand extracted with benzene. After the elimination of the benzene the newbase distils at 180182 C. under 4 mm pressure as a highly refractive oilwhich is viscous at room tem perature, but on standing for several dayssolidifies toa white crystalline mass.

For the production of the dyestufi of the above formula 40 grams of thebase are heated on an oil bath, while constantly stir- I s) zN-OHr-CH:

ring, with grams of phthalic anhydride for 3 to 4 hours at a maximumtemperature of 17 5 C. After cooling the solidified brittle melt ispowdered and advantageously dissolved in nitrobenzene at 7 080 C. Inorder to eliminate any remaining phthalic acid and to set free the dyebase, the solution is extracted several times with sodium carbonatesolution at 40 to 50 C. The nitrobenzene solution is dried, diluted withether and the dyestuff is then precipitated therefrom in the form of itshydrochloride by the addition of ethereal hydrochloric acid as a reddishbrown, hygroscopic powder, which rapidly dissolves in water with a clearRhodamine coloration. 7

For the esterification of the carboxyl group 10 grams of thishydrochloric acid salt are dissolved in 50 grams of absolute alcohol'andhydrochloric acid gas is passed through the solution, at first for oneday While cooling with ice and then for a further day while boiling thesolution. ness in vacuo the salt of the esterified compound is obtained;it is only distinguishable from the starting material by a slightlyyellower coloration of the aqueous solution. However, the correspondingdyestufi' base is more easily solublein nitrobenzene and the colorationof this solution is remarkably much more violet than that of theunesterified base. These properties are sufficiently characteristic todistinguish the esterified dyestuff base from the unesterified base.

Other xanthene compounds can be produced in the same way.

Example 2 on CH3 CH3 Two mols of meta-hydroXy-N-(methyldiethylamino-ethyl) -aminobenzene are boiled together with twomols of a 50% aqueous oxalic acid and one mol of formic aldehyde inalcoholic solution during 24 hours. There upon water is added and thediphenylmethane compound is salted out by potassium carbonate anddissolved in benzene and the benzene is distilled off. The residue isintroduced, While cooling, into 4: parts by Weight of concentratedsulfuric acid and the yellowish-brown solution is heated on the waterbath. It is allowed to cool to 27 C. and oxidized by adding dried sodiumnitrite at 2730 C. while stirring. The acid solution ispoured on ice,and the zinc chloride salt of the dye is isolated, purified and freedfrom (OzHI) :N-CHz-CHg I On evaporating to dryit has a boiling point of184 For the manufacture of meta-hydroxy-V-diethyl-aminoethyl-aminobenzene 109 grams of finely powderedmeta-aminophenol" are heated in 150 cc. ofbe'nzeneto 7 080 C. and, whilestirring, 140 grams of diethylaminoethylchloride are slowly addedthereto. Finally the reaction mixture is heated for about 8 hours on aboiling Water bath. After cooling the reaction mixture is dissolved withwater and ether, the aqueous layer is separated and extracted severaltimes with ether. Then potassium carbonate is added to the aqueoussolution, whereby the new base is set free. The new base is dissolved inether, the solution is dried and the ether is distilled off. The basehas a boiling point of 153 C. under a pressure of 1 mm. For theformation of the xanthene compound 40 grams of the base are meltedtogether with 50 grams of phthalic acid anhydride in the mannerdescribed in Example 1. The powdered melt is dissolved in methylenechloride; from the solution the phthalic acid is extracted by means of apotassium carbonate solution. Then ethereal hydrochloric acid is addedand the hydrochloric acid salt of the xanthene derivative isprecipitated by the addition of ether. It is purified by redissolving inabsolute alcohol and precipitated with dry ether.

Example 1;

. coon (CzHa) zN-CHi- 0H2 104 grams ofmeta-hydroxy-N-diethylaminoethyl-aminobenzene are heated with 7 0 gramsof di-ethylaminoethyl-chloride and 100 'grams of xylene for 8 hours atabout 140 C. in an oil bath. The reaction mixture is dis solved in etherand diluted hydrochloric acid, the aqueous layer is separated and thefree base liberated therefrom by supersaturating the aqueous layer withpotash and extracting the free base with ether. After the elimination ofthe ether the meta-hydroxy-N-bis (diethylaminoethyl) -aminobenzeneremains C. under a pressure of 1 mm.

The formation of the dyestufl' is effected in l the same manner asdescribed in Example 3. A clear bluish-red dyestulf is obtainedthe baseof which is Very easily soluble in organic:

solvents. p I This applicationis a continuation in part of 'ourapplicationSer. No. 52,228, filed Au gust 24, 1925,: (U. st'Patent No.1,766,403).

. We claim:

1. As new. products, the xanthene comwherein X stands for a substituentof the group consisting of hydrogen, alkyl, aminoalkyl andalkylaminoalkyl, R stands for an alkylene residue which may besubstitutedby hydroxyl' groups, R and R stand for alkyl groups which maybe substituted by the amino group, and, n stands for one of thenumbersone and two, and wherein the 7 nuclei may be further substituted, by substituents of the group consisting of alkyl, alkoxy, phenyl,carboxyphenyl ..and. halogen, said compounds being generally watersoluble bronze colored substances,the free bases being generally yellowto red colored, generally sparingly soluble in water, but soluble inorganic solvents. I

2. As a new product, the xanthene compound of the following prob-ableformula:

-OCOOH being a bronze-colored, water soluble substance, the free basebeing a yellowish colored substance, sparing y soluble in Water, solublein organic solvents. I

3. As new products, the xanthene compounds of the'probable formula:

wherein X stands for a substituent of the group consisting of hydrogen,alkyl and dihands and aflix our seals.

alkylamino-alkyl, R stands'for an alkylene WERNER SCHULEMANN. [L. v5.] Aresidue, R and R stand for alkyl groups FRITZ MIETZSCH. [L. s] and Yresprese-nts hydrogen or a phenyl resia] due. containing a carboxylicacid or carboxylic acid ester group, said compounds being generallyWater-soluble, bronze-colored substances, the free bases being generallyyellow to red colored compounds, generally sparingly soluble in water,but soluble in organic solvents.

4. As new products, the Xanthenecompounds of the probable generalformula:

OOO.R

organic solvents.

5. As a new product, the xanthene' compound of the probable formula:

being a bronze-colored, Water-soluble substance, the free base beingsparingly soluble in water, but soluble in organic solvents.

6. As a new product, the Xanthene compound of the probable formula:

(CgHQzN-CHz-OHa CHz-CHz-NUJzHg) 2 N o N a (CzHu) zN-CHrCH: l OHz-CHn-N(CgHg) being a bronze-colored, water-soluble substance, the free basebeing sparingly soluble in water, but soluble in organic solvents.

AUGUST WVINGLER. [1

In testimony whereof, we hereunto setour

